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2.
Cell Syst ; 12(8): 780-794.e7, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34139154

RESUMO

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.


Assuntos
Biomarcadores/análise , COVID-19/patologia , Progressão da Doença , Proteoma/fisiologia , Fatores Etários , Contagem de Células Sanguíneas , Gasometria , Ativação Enzimática , Humanos , Inflamação/patologia , Aprendizado de Máquina , Prognóstico , Proteômica , SARS-CoV-2/imunologia
3.
Ann Intensive Care ; 11(1): 62, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891213

RESUMO

BACKGROUND: Metabolic alkalosis is a frequently occurring problem during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to evaluate the effectiveness of switching from high to low bicarbonate (HCO3-) replacement fluid in alkalotic critically ill patients with acute kidney injury treated by CVVH and RCA. METHODS: A retrospective-comparative study design was applied. Patients who underwent CVVH with RCA in the ICU between 09/2016 and 11/2017 were evaluated. Data were available from the clinical routine. A switch of the replacement fluid Phoxilium® (30 mmol/l HCO3-) to Biphozyl® (22 mmol/l HCO3-) was performed as blood HCO3- concentration persisted ≥ 26 mmol/l despite adjustments of citrate dose and blood flow. Data were collected from 72 h before the switch of the replacement solutions until 72 h afterwards. RESULTS: Of 153 patients treated with CVVH during that period, 45 patients were switched from Phoxilium® to Biphozyl®. Forty-two patients (42 circuits) were available for statistical analysis. After switching the replacement fluid from Phoxilium® to Biphozyl® the serum HCO3- concentration decreased significantly from 27.7 mmol/l (IQR 26.9-28.9) to 25.8 mmol/l (IQR 24.6-27.7) within 24 h (p < 0.001). Base excess (BE) decreased significantly from 4.0 mmol/l (IQR 3.1-5.1) to 1.8 mmol/l (IQR 0.2-3.4) within 24 h (p < 0.001). HCO3- and BE concentration remained stable from 24 h till the end of observation at 72 h after the replacement fluid change (p = 0.225). pH and PaCO2 did not change significantly after the switch of the replacement fluid until 72 h. CONCLUSIONS: This retrospective analysis suggests that for patients developing refractory metabolic alkalosis during CVVH with RCA the use of Biphozyl® reduces external HCO3- load and sustainably corrects intracorporeal HCO3- and BE concentrations. Future studies have to prove whether correcting metabolic alkalosis during CVVH with RCA in critically ill patients is of relevance in terms of clinical outcome.

4.
Br J Anaesth ; 126(3): 590-598, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33422287

RESUMO

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor. METHODS: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT. RESULTS: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test. CONCLUSION: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Estado Terminal/epidemiologia , Fibrinólise/efeitos dos fármacos , Trombofilia/sangue , Trombofilia/epidemiologia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Testes de Coagulação Sanguínea/métodos , COVID-19/diagnóstico , Feminino , Fibrinólise/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombofilia/diagnóstico , Ativador de Plasminogênio Tecidual/administração & dosagem
5.
Wien Klin Wochenschr ; 132(21-22): 653-663, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33170333

RESUMO

INTRODUCTION: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus­2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. METHODS: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. RESULTS: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54-74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49-64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5-11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5-31 days), median hospital LOS was 27 days (IQR 13-49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. CONCLUSION: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Áustria , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/terapia , SARS-CoV-2 , Resultado do Tratamento
7.
Intensive Care Med ; 46(4): 654-672, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31820034

RESUMO

BACKGROUND: Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO). METHODS: A consensus conference on the spectrum of lung-kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function. CONCLUSION: The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung-kidney interactions to improve care processes and outcomes in critical illness.


Assuntos
Injúria Renal Aguda , Estado Terminal , Doença Aguda , Injúria Renal Aguda/terapia , Áustria , Humanos , Rim , Pulmão
8.
J Thorac Dis ; 11(Suppl 3): S325-S328, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30997210
10.
J Nephrol ; 31(6): 855-862, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30298272

RESUMO

Oliguria is often observed in critically ill patients. However, different thresholds in urine output (UO) have raised discussion as to the clinical importance of a transiently reduced UO of less than 0.5 ml/kg/h lasting for at least 6 h. While some studies have demonstrated that isolated oliguria without a concomitant increase in serum creatinine is associated with higher mortality rates, different underlying pathophysiological mechanisms suggest varied clinical importance of reduced UO, as some episodes of oliguria may be fully reversible. We aim to explore the clinical relevance of oliguria in critically ill patients and propose a clinical pathway for the diagnostic and therapeutic management of an oliguric, critically ill patient.


Assuntos
Injúria Renal Aguda/diagnóstico , Rim/fisiopatologia , Oligúria/diagnóstico , Urodinâmica , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Biomarcadores/sangue , Creatinina/sangue , Estado Terminal , Deslocamentos de Líquidos Corporais , Hemodinâmica , Humanos , Testes de Função Renal , Oligúria/mortalidade , Oligúria/fisiopatologia , Oligúria/terapia , Valor Preditivo dos Testes , Terapia de Substituição Renal , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Equilíbrio Hidroeletrolítico
11.
Intensive Care Med ; 44(3): 323-336, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29541790

RESUMO

PURPOSE: Acute kidney injury (AKI) frequently occurs in critically ill patients and often precipitates use of renal replacement therapy (RRT). However, the ideal circumstances for whether and when to start RRT remain unclear. We performed evidence synthesis of the available literature to evaluate the value of biomarkers to predict receipt of RRT for AKI. METHODS: We conducted a PRISMA-guided systematic review and meta-analysis including all trials evaluating biomarker performance for prediction of RRT in AKI. A systematic search was applied in MEDLINE, Embase, and CENTRAL databases from inception to September 2017. All studies reporting an area under the curve (AUC) for a biomarker to predict initiation of RRT were included. RESULTS: Sixty-three studies comprising 15,928 critically ill patients (median per study 122.5 [31-1439]) met eligibility. Forty-one studies evaluating 13 different biomarkers were included. Of these biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) had the largest body of evidence. The pooled AUCs for urine and blood NGAL were 0.720 (95% CI 0.638-0.803) and 0.755 (0.706-0.803), respectively. Blood creatinine and cystatin C had pooled AUCs of 0.764 (0.732-0.796) and 0.768 (0.729-0.807), respectively. For urine biomarkers, interleukin-18, cystatin C, and the product of tissue inhibitor of metalloproteinase-2 and insulin growth factor binding protein-7 showed pooled AUCs of 0.668 (0.606-0.729), 0.722 (0.575-0.868), and 0.857 (0.789-0.925), respectively. CONCLUSION: Though several biomarkers showed promise and reasonable prediction of RRT use for critically ill patients with AKI, the strength of evidence currently precludes their routine use to guide decision-making on when to initiate RRT.


Assuntos
Injúria Renal Aguda , Biomarcadores , Terapia de Substituição Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Proteínas de Fase Aguda , Humanos , Lipocalina-2 , Lipocalinas , Estudos Prospectivos , Proteínas Proto-Oncogênicas , Inibidor Tecidual de Metaloproteinase-2
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